DESCRIPTION: (Principal Investigator's) The primary objective of this research is to continue to discover new strategies for the construction of complex carbocyclic or heterocyclic ring systems. A theme throughout this proposal is the further development and exploitation of new, reactive dienophiles and/or dienes derived from retrocycloaddition reactions of substituted 1,3-dioxins. I is expected that this new methodology will expedite the syntheses of biologically active natural products and/or analogs. Thus, thermolysis of 5-amido-1,3-dioxins will provide 2-amidoacroleins and facilitate the preparation of newly discovered biologically active natural products which embody an aminocyclohexane substructure. For example, the tricyclic ring systems of the recently discovered cytotoxic marine natural product fasicularin and the novel immunosuppressant FR901483 can be rapidly assembled from cycloadducts obtained from this new class of dienophiles and will lead to the first syntheses of these compounds. In addition, the amino-beta,C-glycopyranoside subunit of FR901464, a new anticancer agent possessing a novel mechanism of action, can be readily constructed using this methodology. 2-Acylacroleins can be similarly prepared via retrocycloadditions of 5-acyl-1,3-dioxins. These exceptional heterodienes undergo cycloadditions with enol ethers to afford 5-acyl-3,4-dihydropyrans, a substructural unit embodied in numerous natural products. This methodology will permit the first syntheses of cytotoxic marine natural products such as euplotin C. Another marine natura product, the antimitotic acalycixeniolide B will be synthesized using previously developed methodology and will constitute the first synthesis of a member of the xenicane class of compounds.